The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease

Abstract

3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce biliary cholesterol saturation index (CSI) in duodenal bile in hypercholesterolemic patients and might be useful for gallstone dissolution. However, preliminary data suggest that these drugs are not effective in this respect. We therefore studied 33 patients with radiolucent gallstones in an opacifying gallbladder who were scheduled for elective cholecystectomy. Patients were treated with 40 mg pravastatin day −1 or placebo during the 3 weeks before surgery. Six patients could not be evaluated. Baseline characteristics (age, sex, body mass index, serum cholesterol, and the solitary/multiple gallstone ratio) were similar in both groups. Serum cholesterol fell by 39% in the pravastatin group ( P < .001) and remained unchanged in the placebo group. Biliary cholesterol (9.5 ± 1.3 vs. 14.3 ± 1.5 mmol/L, P = .026), and phospholipid concentrations (24.8 ± 3.9 vs. 36.7 ± 3.9 mmol/L, P = .043) were lower in the pravastatin group. Although bile salt concentrations were lower in the pravastatin group (114 ± 21 vs. 152 ± 15 mmol/L), this difference was not significant. CSI was not different between both groups (142 ± 27% [pravastatin]vs. 113 ± 6% [placebo], P = NS). Cholesterol crystals were present in fresh bile in 7 of 13 patients in the pravastatin group and in 11 of 14 controls ( P = NS). Nucleation time was comparable between the 2 groups (13 ± 3 vs. 9 ± 3 days, P = NS). Bile salt species and molecular species of phospholipids determined with high-performance liquid chromatography did not differ either between both groups. Not only cholesterol but also phospholipid concentrations decrease in gallbladder bile during pravastatin treatment in cholesterol gallstone patients, with comparable CSI and nucleation time. This study does not support the use of HMG-CoA reductase inhibitors for dissolution of cholesterol gallstones.